3.3. Abnormal Accumulation of mtROS is Involved in VSMC-Derived
Foam Cell Necroptosis
Phosphorylation of RIP1 and RIP3 is necessary for necroptosis
activation. Han et al. reported that mtROS promoted RIP1
autophosphorylation and were essential for RIP3 recruitment into the
necrosomes [9]. Other studies have illustrated that the
mitochondrial permeability transition pore (mPTP) opening is essential
for RIP3-mediated necroptosis [13,14], as it is a consequence of
mitochondrial potential collapse. To elucidate the mechanism underlying
ox-LDL-induced VSMC-derived foam cell necroptosis, we incubated VSMCs
with an ROS scavenger,
Tempol, before treatment with
ox-LDL. After incubation with Tempol, the generation of mtROS induced by
ox-LDL in VSMC-derived foam cells was reduced (Fig. 3a) and the loss of
ΔΨm was also effectively inhibited (Fig. 3b). To further characterize
the effect of Tempol on ox-LDL-induced cell necroptosis, the PI-positive
cells were examined using flow cytometry. Following pre-incubation with
Tempol, the number of ox-LDL-induced PI-positive cells was significantly
reduced (Fig. 3c). These results suggest abnormal accumulation of mtROS
as a potential mechanism underlying ox-LDL-induced cell necroptosis.